SK9592000A3 - Triazine compounds for treatment of cns disorders - Google Patents

Triazine compounds for treatment of cns disorders Download PDF

Info

Publication number: SK9592000A3
Authority: SK; Slovakia
Prior art keywords: formula; compound; compounds; triazine; pharmaceutically acceptable
Prior art date: 1997-12-22

Application number

SK959-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Brian Cox

Mark Patrick Healy

Malcolm Stuart Nobbs

Gita Punjabhai Shah

Original Assignee

Glaxo Group Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-12-22

Filing date

1998-12-18

Publication date

2001-03-12

1998-12-18 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

2001-03-12 Publication of SK9592000A3 publication Critical patent/SK9592000A3/sk

Links

150000003918 triazines Chemical class 0.000 title claims 12
150000001875 compounds Chemical class 0.000 claims abstract description 99
238000000034 method Methods 0.000 claims description 21
239000008194 pharmaceutical composition Substances 0.000 claims description 18
208000002193 Pain Diseases 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
208000020925 Bipolar disease Diseases 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
206010015037 epilepsy Diseases 0.000 claims description 8
208000035475 disorder Diseases 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
230000004770 neurodegeneration Effects 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 4
208000028683 bipolar I disease Diseases 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
208000015122 neurodegenerative disease Diseases 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
206010012335 Dependence Diseases 0.000 claims description 2
230000004112 neuroprotection Effects 0.000 claims 2
230000001939 inductive effect Effects 0.000 claims 1
230000003647 oxidation Effects 0.000 claims 1
238000007254 oxidation reaction Methods 0.000 claims 1
150000003839 salts Chemical class 0.000 abstract description 7
239000012453 solvate Substances 0.000 abstract description 2
229940002612 prodrug Drugs 0.000 abstract 1
239000000651 prodrug Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
239000000203 mixture Substances 0.000 description 35
239000000243 solution Substances 0.000 description 26
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000003826 tablet Substances 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
239000007787 solid Substances 0.000 description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
206010010904 Convulsion Diseases 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
239000004480 active ingredient Substances 0.000 description 11
239000002775 capsule Substances 0.000 description 11
239000003921 oil Substances 0.000 description 11
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 9
239000000047 product Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
238000012360 testing method Methods 0.000 description 9
229960001848 lamotrigine Drugs 0.000 description 8
239000007788 liquid Substances 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
239000004615 ingredient Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
201000010099 disease Diseases 0.000 description 6
239000003480 eluent Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 5
KNVKRFZYVIDXMA-UHFFFAOYSA-N 2,3,5-trichlorobenzoyl cyanide Chemical compound ClC1=CC(Cl)=C(Cl)C(C(=O)C#N)=C1 KNVKRFZYVIDXMA-UHFFFAOYSA-N 0.000 description 5
101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 5
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
210000003169 central nervous system Anatomy 0.000 description 5
239000012458 free base Substances 0.000 description 5
239000008187 granular material Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
230000002265 prevention Effects 0.000 description 5
230000009467 reduction Effects 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
239000008215 water for injection Substances 0.000 description 5
239000008096 xylene Substances 0.000 description 5
XQHHKDYGFGXLMM-UHFFFAOYSA-N C[S+]=C(N)NN.I Chemical compound C[S+]=C(N)NN.I XQHHKDYGFGXLMM-UHFFFAOYSA-N 0.000 description 4
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000012267 brine Substances 0.000 description 4
239000000969 carrier Substances 0.000 description 4
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
208000002551 irritable bowel syndrome Diseases 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000008213 purified water Substances 0.000 description 4
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
239000000829 suppository Substances 0.000 description 4
229940124597 therapeutic agent Drugs 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
-1 triazine compound Chemical class 0.000 description 4
ZJHSAOIYBRFAKE-UHFFFAOYSA-N 2-oxo-2-(2,3,5-trichlorophenyl)acetamide Chemical compound NC(=O)C(=O)C1=CC(Cl)=CC(Cl)=C1Cl ZJHSAOIYBRFAKE-UHFFFAOYSA-N 0.000 description 3
OYRPBDIPZVZBIA-UHFFFAOYSA-N C[S+]=C(N)NN Chemical class C[S+]=C(N)NN OYRPBDIPZVZBIA-UHFFFAOYSA-N 0.000 description 3
108091006146 Channels Proteins 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
229920000168 Microcrystalline cellulose Polymers 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
239000001961 anticonvulsive agent Substances 0.000 description 3
239000000679 carrageenan Substances 0.000 description 3
235000010418 carrageenan Nutrition 0.000 description 3
229920001525 carrageenan Polymers 0.000 description 3
229940113118 carrageenan Drugs 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
238000009472 formulation Methods 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000000463 material Substances 0.000 description 3
229940016286 microcrystalline cellulose Drugs 0.000 description 3
235000019813 microcrystalline cellulose Nutrition 0.000 description 3
239000008108 microcrystalline cellulose Substances 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
CGFDSIZRJWMQPP-UHFFFAOYSA-N 2,3,5-trichlorobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC(Cl)=C1Cl CGFDSIZRJWMQPP-UHFFFAOYSA-N 0.000 description 2
ZXHSKMRJXAOBQL-UHFFFAOYSA-N 2,3,5-trichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC(Cl)=CC(Cl)=C1Cl ZXHSKMRJXAOBQL-UHFFFAOYSA-N 0.000 description 2
KUWPCJHYPSUOFW-UHFFFAOYSA-N 2-(hydroxymethyl)-6-(2-nitrophenoxy)oxane-3,4,5-triol Chemical compound OC1C(O)C(O)C(CO)OC1OC1=CC=CC=C1[N+]([O-])=O KUWPCJHYPSUOFW-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
GQAGSZGQRVMXTD-UHFFFAOYSA-N 6-(2,3,5-trichlorophenyl)-1,2,4-triazin-5-amine Chemical compound NC1=NC=NN=C1C1=CC(Cl)=CC(Cl)=C1Cl GQAGSZGQRVMXTD-UHFFFAOYSA-N 0.000 description 2
206010003591 Ataxia Diseases 0.000 description 2
229920003084 Avicel® PH-102 Polymers 0.000 description 2
CMPADKUEQHPXAM-UHFFFAOYSA-N CC=1NN(C(=C(N1)N)C1=C(C(=CC(=C1)Cl)Cl)Cl)OS(=O)(=O)O Chemical compound CC=1NN(C(=C(N1)N)C1=C(C(=CC(=C1)Cl)Cl)Cl)OS(=O)(=O)O CMPADKUEQHPXAM-UHFFFAOYSA-N 0.000 description 2
HDNKZEPATYGLKR-UHFFFAOYSA-N C[S+]=C(N)NN=C(C1=CC(Cl)=CC(Cl)=C1Cl)C#N Chemical compound C[S+]=C(N)NN=C(C1=CC(Cl)=CC(Cl)=C1Cl)C#N HDNKZEPATYGLKR-UHFFFAOYSA-N 0.000 description 2
208000000094 Chronic Pain Diseases 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
229920000881 Modified starch Polymers 0.000 description 2
208000018737 Parkinson disease Diseases 0.000 description 2
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 2
208000004550 Postoperative Pain Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
241000700159 Rattus Species 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
230000000202 analgesic effect Effects 0.000 description 2
229940035676 analgesics Drugs 0.000 description 2
239000000730 antalgic agent Substances 0.000 description 2
230000001773 anti-convulsant effect Effects 0.000 description 2
229940125681 anticonvulsant agent Drugs 0.000 description 2
239000002585 base Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
229940075614 colloidal silicon dioxide Drugs 0.000 description 2
239000007891 compressed tablet Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
239000012043 crude product Substances 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
229960003638 dopamine Drugs 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
235000019197 fats Nutrition 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
238000001802 infusion Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
208000004296 neuralgia Diseases 0.000 description 2
229960005152 pentetrazol Drugs 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
229920000728 polyester Polymers 0.000 description 2
229920001296 polysiloxane Polymers 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000002243 precursor Substances 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000002002 slurry Substances 0.000 description 2
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
235000010234 sodium benzoate Nutrition 0.000 description 2
239000004299 sodium benzoate Substances 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
229920003109 sodium starch glycolate Polymers 0.000 description 2
229940079832 sodium starch glycolate Drugs 0.000 description 2
239000008109 sodium starch glycolate Substances 0.000 description 2
235000010265 sodium sulphite Nutrition 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
231100001274 therapeutic index Toxicity 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
239000003039 volatile agent Substances 0.000 description 2
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
XGCDBGRZEKYHNV-UHFFFAOYSA-N 1,1-bis(diphenylphosphino)methane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CP(C=1C=CC=CC=1)C1=CC=CC=C1 XGCDBGRZEKYHNV-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
YUCRNASRVPZKNQ-UHFFFAOYSA-N 2-chlorobenzoyl cyanide Chemical compound ClC1=CC=CC=C1C(=O)C#N YUCRNASRVPZKNQ-UHFFFAOYSA-N 0.000 description 1
MKIFUXUMQPXNAA-UHFFFAOYSA-N 2h-triazine-1,5-diamine Chemical class NN1NN=CC(N)=C1 MKIFUXUMQPXNAA-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
208000004998 Abdominal Pain Diseases 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
206010003628 Atonic seizures Diseases 0.000 description 1
206010006298 Breast pain Diseases 0.000 description 1
206010053398 Clonic convulsion Diseases 0.000 description 1
208000033001 Complex partial seizures Diseases 0.000 description 1
239000004821 Contact adhesive Substances 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
208000020401 Depressive disease Diseases 0.000 description 1
241000400611 Eucalyptus deanei Species 0.000 description 1
208000001640 Fibromyalgia Diseases 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
208000003078 Generalized Epilepsy Diseases 0.000 description 1
208000034308 Grand mal convulsion Diseases 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
208000004454 Hyperalgesia Diseases 0.000 description 1
208000035154 Hyperesthesia Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
208000006662 Mastodynia Diseases 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
208000026072 Motor neurone disease Diseases 0.000 description 1
208000000112 Myalgia Diseases 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
206010056677 Nerve degeneration Diseases 0.000 description 1
206010029350 Neurotoxicity Diseases 0.000 description 1
208000037158 Partial Epilepsies Diseases 0.000 description 1
206010034759 Petit mal epilepsy Diseases 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
208000034189 Sclerosis Diseases 0.000 description 1
206010040703 Simple partial seizures Diseases 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
108010052164 Sodium Channels Proteins 0.000 description 1
102000018674 Sodium Channels Human genes 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
208000020339 Spinal injury Diseases 0.000 description 1
108010022394 Threonine synthase Proteins 0.000 description 1
206010043994 Tonic convulsion Diseases 0.000 description 1
206010044221 Toxic encephalopathy Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
208000028311 absence seizure Diseases 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000036982 action potential Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
208000005298 acute pain Diseases 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
LSNWBKACGXCGAJ-UHFFFAOYSA-N ampiroxicam Chemical group CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OCC)=C1C(=O)NC1=CC=CC=N1 LSNWBKACGXCGAJ-UHFFFAOYSA-N 0.000 description 1
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000003556 anti-epileptic effect Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
229960003965 antiepileptics Drugs 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000000022 bacteriostatic agent Substances 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
208000029028 brain injury Diseases 0.000 description 1
239000000872 buffer Substances 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
239000003874 central nervous system depressant Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000007910 chewable tablet Substances 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
229960003920 cocaine Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000012050 conventional carrier Substances 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
210000001653 corpus striatum Anatomy 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
208000010643 digestive system disease Diseases 0.000 description 1
102000004419 dihydrofolate reductase Human genes 0.000 description 1
JZBWUTVDIDNCMW-UHFFFAOYSA-L dipotassium;oxido sulfate Chemical compound [K+].[K+].[O-]OS([O-])(=O)=O JZBWUTVDIDNCMW-UHFFFAOYSA-L 0.000 description 1
238000007907 direct compression Methods 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
229940079593 drug Drugs 0.000 description 1
201000006549 dyspepsia Diseases 0.000 description 1
201000009028 early myoclonic encephalopathy Diseases 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
201000003104 endogenous depression Diseases 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
208000018685 gastrointestinal system disease Diseases 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
229930193405 glaucone Natural products 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
201000001993 idiopathic generalized epilepsy Diseases 0.000 description 1
238000002513 implantation Methods 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
208000002780 macular degeneration Diseases 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
208000024714 major depressive disease Diseases 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000000155 melt Substances 0.000 description 1
239000012528 membrane Substances 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
208000005264 motor neuron disease Diseases 0.000 description 1
238000000465 moulding Methods 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
208000013465 muscle pain Diseases 0.000 description 1
208000021722 neuropathic pain Diseases 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
230000007135 neurotoxicity Effects 0.000 description 1
231100000228 neurotoxicity Toxicity 0.000 description 1
229960002715 nicotine Drugs 0.000 description 1
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
229940127240 opiate Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
238000006303 photolysis reaction Methods 0.000 description 1
230000015843 photosynthesis, light reaction Effects 0.000 description 1
229920000058 polyacrylate Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920000098 polyolefin Polymers 0.000 description 1
229920002635 polyurethane Polymers 0.000 description 1
239000004814 polyurethane Substances 0.000 description 1
229920002689 polyvinyl acetate Polymers 0.000 description 1
239000011118 polyvinyl acetate Substances 0.000 description 1
239000011148 porous material Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003368 psychostimulant agent Substances 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000011160 research Methods 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
238000007493 shaping process Methods 0.000 description 1
229920005573 silicon-containing polymer Polymers 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229940125794 sodium channel blocker Drugs 0.000 description 1
239000003195 sodium channel blocking agent Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002889 sympathetic effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VCSJAJFSKJCWFG-UHFFFAOYSA-N triazin-5-amine Chemical class NC1=CN=NN=C1 VCSJAJFSKJCWFG-UHFFFAOYSA-N 0.000 description 1
206010044652 trigeminal neuralgia Diseases 0.000 description 1
WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000010937 tungsten Substances 0.000 description 1
230000000007 visual effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D253/075—Two hetero atoms, in positions 3 and 5
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Addiction (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

SK959-2000A 1997-12-22 1998-12-18 Triazine compounds for treatment of cns disorders SK9592000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9726987.2A GB9726987D0 (en)	1997-12-22	1997-12-22	Compounds
PCT/EP1998/008273 WO1999032462A1 (en)	1997-12-22	1998-12-18	Triazine compounds for treatment of cns disorders

Publications (1)

Publication Number	Publication Date
SK9592000A3 true SK9592000A3 (en)	2001-03-12

Family

ID=10823992

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK959-2000A SK9592000A3 (en)	1997-12-22	1998-12-18	Triazine compounds for treatment of cns disorders

Country Status (34)

Country	Link
US (2)	US6265405B1 (id)
EP (1)	EP1042304A1 (id)
JP (1)	JP2001526275A (id)
KR (1)	KR20010024800A (id)
CN (1)	CN1284951A (id)
AP (1)	AP2000001846A0 (id)
AR (1)	AR014146A1 (id)
AU (1)	AU753874B2 (id)
BR (1)	BR9814495A (id)
CA (1)	CA2315620A1 (id)
CO (1)	CO5011066A1 (id)
EA (1)	EA200000561A1 (id)
EE (1)	EE200000391A (id)
GB (1)	GB9726987D0 (id)
GT (1)	GT199800203A (id)
HN (1)	HN1998000193A (id)
HR (1)	HRP20000419A2 (id)
HU (1)	HUP0100611A3 (id)
ID (1)	ID25449A (id)
IL (1)	IL136867A0 (id)
IS (1)	IS5542A (id)
JO (1)	JO2065B1 (id)
MA (1)	MA26587A1 (id)
NO (1)	NO20003211L (id)
NZ (1)	NZ505254A (id)
PA (1)	PA8465101A1 (id)
PE (1)	PE20000063A1 (id)
PL (1)	PL341392A1 (id)
SK (1)	SK9592000A3 (id)
SV (1)	SV1998000151A (id)
TR (1)	TR200001970T2 (id)
WO (1)	WO1999032462A1 (id)
YU (1)	YU39600A (id)
ZA (1)	ZA9811725B (id)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0002666D0 (en)	2000-02-04	2000-03-29	Univ London	Blockade of voltage dependent sodium channels
ES2286328T3 (es) *	2001-12-27	2007-12-01	Ortho-Mcneil Pharmaceutical, Inc.	Aroilpirrolheteroaril y metanoles utiles para tratar transtornos del sistema nervioso central.
CN100363007C (zh) *	2002-07-29	2008-01-23	葛兰素集团有限公司	含拉莫三嗪的缓释制剂
JP2006515326A (ja) *	2003-01-30	2006-05-25	ダイノジェンファーマシューティカルズ，インコーポレイテッド	胃腸管障害を処置するためのナトリウムチャネルモジュレーターの使用
MY142651A (en)	2003-03-18	2010-12-15	Merck Sharp & Dohme	Biaryl substituted triazoles as sodium channel blockers
DE10332472A1 (de) *	2003-07-16	2005-02-03	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Ambroxol für die Behandlung von Tinnitus
ES2339021T3 (es) *	2003-08-25	2010-05-14	Newron Pharmaceuticals S.P.A.	Derivados de alfa-aminoamida utiles como agentes antiinflamatorios.
US20060115865A1 (en) *	2004-10-25	2006-06-01	Anlong Ouyang	Lamotrigine analogs
GB201111712D0 (en)	2011-07-08	2011-08-24	Gosforth Ct Holdings Pty Ltd	Pharmaceutical compositions
TWI651310B (zh)	2014-02-20	2019-02-21	日商日本煙草產業股份有限公司	三化合物及其醫藥用途
TWI704139B (zh)	2015-08-17	2020-09-11	日商日本煙草產業股份有限公司	羥基三化合物及其醫藥用途
EP3524605B1 (en) *	2018-02-13	2019-11-27	F.I.S.- Fabbrica Italiana Sintetici S.p.A.	New efficient process for the preparation of sitagliptin
CN114796146B (zh) *	2022-04-28	2023-03-28	上海奥科达医药科技股份有限公司	一种拉莫三嗪的缓释制剂及其制备方法

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3637688A (en)	1970-01-09	1972-01-25	American Home Prod	6-(fluoro and trifluoromethyl phenyl)-3 5-diamino - 1 2 4 - triazines and substituted - 6 - phenylalkyl-3,5-diamino-1 2 4-triazines
JPS5625170A (en)	1979-06-01	1981-03-10	Wellcome Found	Triazine derivative
EP0021121B1 (en) *	1979-06-01	1983-05-11	The Wellcome Foundation Limited	1,2,4-triazine derivatives, process for preparing such compounds and pharmaceutical compositions containing them
IT1145308B (it)	1979-08-16	1986-11-05	Wellcome Found	Composti aromatici sostituiti
GB8328757D0 (en)	1983-10-27	1983-11-30	Wellcome Found	Chemical compounds
GB9012311D0 (en)	1990-06-01	1990-07-18	Wellcome Found	Pharmacologically active cns compounds
GB9012312D0 (en)	1990-06-01	1990-07-18	Wellcome Found	Pharmacologically active cns compounds
GB9012316D0 (en)	1990-06-01	1990-07-18	Wellcome Found	Pharmacologically active cns compounds
GB9203483D0 (en)	1992-02-19	1992-04-08	Wellcome Found	Anti-inflammatory compounds
AU688729B2 (en)	1992-06-12	1998-03-19	Wellcome Foundation Limited, The	Use of 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine isethionate for the treatment and prevention of dependence, tolerance and sensitization of drugs
JPH08504798A (ja)	1992-12-18	1996-05-21	ザウエルカムファウンデーションリミテッド	酵素阻害薬としての，ピリミジン，ピリジン，プテリジノンおよびインダゾール誘導体
US5866597A (en)	1993-03-19	1999-02-02	Glaxo Wellcome Inc.	Use of triazine compounds for the treatment of memory and learning disorders
GB9305692D0 (en)	1993-03-19	1993-05-05	Wellcome Found	Therapeutic triazine compounds and use
GB9426448D0 (en) *	1994-12-30	1995-03-01	Wellcome Found	Process
FR2741879A1 (fr)	1995-12-05	1997-06-06	Esteve Labor Dr	Derives de fluorophenyl-triazines et pyrimidines, leur preparation et leur application en tant que medicament

1997
- 1997-12-22 GB GBGB9726987.2A patent/GB9726987D0/en not_active Ceased
1998
- 1998-12-18 CA CA002315620A patent/CA2315620A1/en not_active Abandoned
- 1998-12-18 EP EP98966635A patent/EP1042304A1/en not_active Withdrawn
- 1998-12-18 HU HU0100611A patent/HUP0100611A3/hu unknown
- 1998-12-18 BR BR9814495-2A patent/BR9814495A/pt not_active IP Right Cessation
- 1998-12-18 CO CO98075403A patent/CO5011066A1/es unknown
- 1998-12-18 PL PL98341392A patent/PL341392A1/xx unknown
- 1998-12-18 HR HR20000419A patent/HRP20000419A2/hr not_active Application Discontinuation
- 1998-12-18 AR ARP980106526A patent/AR014146A1/es not_active Application Discontinuation
- 1998-12-18 TR TR2000/01970T patent/TR200001970T2/xx unknown
- 1998-12-18 YU YU39600A patent/YU39600A/sh unknown
- 1998-12-18 EE EEP200000391A patent/EE200000391A/xx unknown
- 1998-12-18 NZ NZ505254A patent/NZ505254A/en unknown
- 1998-12-18 AU AU24147/99A patent/AU753874B2/en not_active Ceased
- 1998-12-18 WO PCT/EP1998/008273 patent/WO1999032462A1/en not_active Ceased
- 1998-12-18 US US09/582,058 patent/US6265405B1/en not_active Expired - Fee Related
- 1998-12-18 ID IDW20001416A patent/ID25449A/id unknown
- 1998-12-18 EA EA200000561A patent/EA200000561A1/ru unknown
- 1998-12-18 JP JP2000525399A patent/JP2001526275A/ja active Pending
- 1998-12-18 AP APAP/P/2000/001846A patent/AP2000001846A0/en unknown
- 1998-12-18 SV SV1998000151A patent/SV1998000151A/es unknown
- 1998-12-18 SK SK959-2000A patent/SK9592000A3/sk unknown
- 1998-12-18 CN CN98813745A patent/CN1284951A/zh active Pending
- 1998-12-18 IL IL13686798A patent/IL136867A0/xx unknown
- 1998-12-18 KR KR1020007006947A patent/KR20010024800A/ko not_active Withdrawn
- 1998-12-21 JO JO19982065A patent/JO2065B1/en active
- 1998-12-21 PA PA19988465101A patent/PA8465101A1/es unknown
- 1998-12-21 ZA ZA9811725A patent/ZA9811725B/xx unknown
- 1998-12-21 PE PE1998001255A patent/PE20000063A1/es not_active Application Discontinuation
- 1998-12-22 MA MA25403A patent/MA26587A1/fr unknown
- 1998-12-22 GT GT199800203A patent/GT199800203A/es unknown
1999
- 1999-12-21 HN HN1998000193A patent/HN1998000193A/es unknown
2000
- 2000-06-20 IS IS5542A patent/IS5542A/is unknown
- 2000-06-21 NO NO20003211A patent/NO20003211L/no unknown
2001
- 2001-07-06 US US09/899,198 patent/US6465461B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
NO20003211L (no)	2000-08-21
HUP0100611A2 (hu)	2001-09-28
US6265405B1 (en)	2001-07-24
AU2414799A (en)	1999-07-12
ZA9811725B (en)	2000-06-27
GT199800203A (es)	2000-06-14
IS5542A (is)	2000-06-20
WO1999032462A1 (en)	1999-07-01
AR014146A1 (es)	2001-02-07
AP2000001846A0 (en)	2000-06-30
IL136867A0 (en)	2001-06-14
NZ505254A (en)	2002-06-28
GB9726987D0 (en)	1998-02-18
HN1998000193A (es)	2000-04-05
ID25449A (id)	2000-10-05
EA200000561A1 (ru)	2001-04-23
EE200000391A (et)	2002-02-15
SV1998000151A (es)	1999-07-05
NO20003211D0 (no)	2000-06-21
EP1042304A1 (en)	2000-10-11
CA2315620A1 (en)	1999-07-01
HRP20000419A2 (en)	2000-12-31
PA8465101A1 (es)	2000-09-29
AU753874B2 (en)	2002-10-31
TR200001970T2 (tr)	2001-01-22
CO5011066A1 (es)	2001-02-28
PE20000063A1 (es)	2000-02-16
US6465461B1 (en)	2002-10-15
MA26587A1 (fr)	2004-12-20
JO2065B1 (en)	2000-05-21
HUP0100611A3 (en)	2003-03-28
JP2001526275A (ja)	2001-12-18
CN1284951A (zh)	2001-02-21
YU39600A (sh)	2002-11-15
KR20010024800A (ko)	2001-03-26
BR9814495A (pt)	2000-10-10
PL341392A1 (en)	2001-04-09

Publication	Publication Date	Title
EP2703396B1 (en)	2016-06-22	Inhibitor of sodium-dependent glucose transport protein and preparation method therefor and use thereof
EP3833670A1 (en)	2021-06-16	6-(4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-(2,3-dichlorophenyl)-2-methylpyrimidin-4(3h)-one derivatives and related compounds as ptpn11 (shp2) inhibitors for treating cancer
KR102171120B1 (ko)	2020-10-29	치환된 2-티옥소-이미다졸리딘-4-온 및 이의 스피로 유사체, 전립선암 치료용 항암 활성 성분, 약학적 조성물, 약제 제조 방법 및 치료 방법
US6265405B1 (en)	2001-07-24	Triazine compounds for treatment of CNS disorders
US20170143708A1 (en)	2017-05-25	Compounds, compositions and methods of agelastatin alkaloids
RU2519546C1 (ru)	2014-06-10	КОНЪЮГАТЫ И МАЛЫЕ МОЛЕКУЛЫ, ВЗАИМОДЕЙСТВУЮЩИЕ С РЕЦЕПТОРОМ CD16а
JP2007510741A (ja)	2007-04-26	ナトリウムチャンネル遮断薬としての置換トリアゾール類
SK287794B6 (sk)	2011-10-04	Laktámová zlúčenina, spôsob jej prípravy a použitie ako liečivo
JPH0372467A (ja)	1991-03-27	ピペラジン誘導体
EP4606798A1 (en)	2025-08-27	Benzoisothiazole compound, and pharmaceutical composition and use thereof
KR20010079696A (ko)	2001-08-22	피라진 화합물
EP3004116B1 (en)	2018-01-03	Tetrahydro-2h-pyrano[3,2-c]isochromene-6-ones and analogs for the treatment of inflammatory disorders
HUT60726A (en)	1992-10-28	Process for producing 3,5-diamino-6-(4-aminochlorophenyl)-1,2,4-triazine derivatives acting on central nervous system, and pharmaceutical compositions comprising such compounds
JP2024535745A (ja)	2024-10-02	Ａｍｐｋ活性化剤として有用なチアジアゾロン誘導体
EP4305026B1 (en)	2025-05-07	Anti-inflammatory carboxamide derivatives
CZ20002361A3 (cs)	2000-11-15	Triazinové deriváty
CN100569740C (zh)	2009-12-16	N-or酰胺类化合物,其制备方法和其应用
SK278141B6 (en)	1996-02-07	Enolether amide 1,1-dioxo-6-chloro-4-hydroxy-2-methyl-n- -(2-pyridyl)-2h-thieno(2,3-e)1,2-thiazine-3-carboxylic acid, method of its production and pharmaceutical agent
MXPA00006223A (en)	2001-06-26	Triazine compounds for treatment of cns disorders
EP3074379B1 (en)	2019-06-26	Opioid agonists and uses thereof
JP2000500455A (ja)	2000-01-18	血液調節化合物
US20120165315A1 (en)	2012-06-28	Meptazinol carbamate prodrug salts
JPH1160484A (ja)	1999-03-02	Ｔｎｆ産生阻害剤
JP7274473B2 (ja)	2023-05-16	４－アミノピリミジン化合物の合成
KR101072698B1 (ko)	2011-10-11	신규 메트로니다졸 전구체 화합물 및 이를 유효성분으로 함유하는 약학조성물